Timing-dependent anti-inflammatory effects of empagliflozin in monocyte-derived macrophages from post-myocardial infarct patients with type 2 diabetes
Abstract
Background and objective: Inflammation drives early recurrent cardiovascular risk in type 2 diabetes mellitus (T2DM) patients following acute myocardial infarction (AMI), particularly within 30-90 days post-discharge. Sodium-glucose co-transporter 2 (SGLT2) inhibitors such as empagliflozin (EMPA) provide cardiometabolic benefits, but their anti-inflammatory effects and optimal timing after AMI remain unclear. Given the prognostic role of systemic markers like the neutrophil-to-lymphocyte ratio, we investigated whether early initiation of EMPA modulates NOD-like receptor protein-3 (NLRP3) inflammasome activity and inflammatory responses in monocyte-derived macrophages (MDMs) from T2DM-AMI patients.
Methods: Sixty-six participants were randomised to receive EMPA either at discharge (Arm-A) or following a 90-day delay (Arm B). Clinical data and biological samples were collected over 180 days. CD14+ MDMs and plasma were obtained at days 0, 30, and 90 (EMPA vs. no EMPA), and days 90, 120, and 180 (early vs. delayed). Inflammatory and metabolic markers were assessed using RT-qPCR, luminescence-based caspase-1 and ATP assays, and targeted immunoassays.
Results: Early EMPA administration was associated with reduced NLRP3 priming (IL1β mRNA) and activation (caspase-1 activity), potentially linked to decreased release of ATP, a danger associated molecular pattern (DAMP). In the absence of EMPA, pro-inflammatory cytokines (TNFα, IL6, MCP1) and M1 macrophage markers (e.g., CD80) either…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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